Derivatives of 2-methylenepropane-1,3-diol as new antagonists of platelet activating factor

Abstract

Two new achiral platelet activating factor (PAF) antagonists, N-[5-[[2-methylene-3- [[(octadecylamino)carbonyl]oxy]propoxy]carbonyl]pentyl]pyridinium bromide and 3-[6-[[2-methylene-3- [[(octadecylamino)carbonyl]oxy]propoxy]carbonyl]hexyl]thiazolium bromide were synthesized from 2-methylenepropane-1,3-diol. Platelet aggregation in platelet-rich plasma from rabbits, induced by racemic C16-PAF, was competitively antagonized by 9 or 10. At concentrations less than or equal to 10(-4) M, neither compound 9 nor compound 10 caused platelet aggregation, nor did they inhibit platelet aggregation induced by collagen or adenosine diphosphate. Bronchoconstriction in the guinea pig and hypotension in the rat, induced by racemic C16-PAF, were also effectively antagonized by 9 and 10. Both appear to be more potent as PAF antagonists than Takeda's CV-3988.

Catalytic Allylic Chlorination of Natural Terpenic Olefins Using Supported and Nonsupported Lewis Acid Catalysts

“…As vinyl chloride derivatives represent great interest in organic synthesis and biological activity [38,48,49], this procedure may serve as a tool for their synthesis in a simple one step. All isolated pure products were fully characterized by 1 H, 13 C NMR, and mass spectroscopy (Supporting Information, Figures S1-S41).…”

“…e pure chlorinated products were obtained by column chromatography over silica gel using hexane and ethyl acetate as eluents. e isolated pure products were fully characterized by 1 H, 13 C NMR, and GC-MS. ( Figure S4: 1H NMR spectrum of product c. Figure S5: APT spectrum of product c. Figure S6: MS spectrum of product c. Figure S7: 1H NMR spectrum of product e. Figure S8: APT spectrum of product e. Figure S9: MS spectrum of product e. Figure S10: 1H NMR spectrum of the limonene oxide monochloride. Figure S11: 13C spectrum of the limonene oxide monochloride.…”

“…Among the versatile natural products bearing these groups, terpenes represent a sustainable supply of intermediates for several functionalization segments of the fine chemical industry, for example, the manufacture of flavors and fragrances [6][7][8]. Allylic chlorination represents a convenient way to functionalize terpenes bearing an allyl, vinyl, or isopropenyl group since further manipulation on the chloride may lead to several functional groups for the synthesis of natural products [9][10][11][12][13]. Previously, we have reported the allylic substitution of optically active natural terpenic allylic chloride derivatives in good yields [14,15].…”

InCl3/NaClO: A reagent for allylic chlorination of terminal olefins

“…[1][2][3][4][5][6] These compounds are usually prepared from the corresponding allylic alcohols by the action of a variety of reagents, such as hydrochloric acid, 7 thionyl chloride, 8 titanium (IV) chloride, 9 N-chlorosuccinimide, 10 methanesulfonyl chloride/lithium chloride, 11 or chloromethylsilanes. 12 Allylic chlorination is a convenient alternative method of terminal olefin functionalization.…”

Σύνθεση αναλόγων του PAF και συσχέτιση της χημικής δομής του μορίου με την βιολογική δραστικότητα in vitro και in vino.

“…Το δραστικότερο συστατικό της σειράς είναι το SRI 63-441 το οποίο αναστέλλει όλες τις κύριες φυσιολογικές αντιδράσεις στους επίμυες, στον ινδόχοιρο, στους σκύλους και στα πρωτόγονα ανθρωποειδή [193]. = 0,l mg/kg IV) και είναι δυο φορές πιο δραστική από την Ι και 35 φορές πιο δραστική από το CV-3988 [170], Τέλος και τα δυο παράγωγα των 2-μεθυλενο-προπανο-1,3-διολών αναστέλλουν την υποτασική δράση του PAF στους επίμυες (ED 5 o=0,5 mg/Kg, IV).…”